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as a result, hyperpolarizes smooth muscle cell membranes. O u a b a i n in low concentrations selectively contracts h u m a n , m o n k e y and dog cerebral arteries, possibly due to i n h i b i t i o n of m e m b r a n e ATPase or Na + p u m p , b u t not secondarily to a release of n o r e p i n e p h r i n e from adrenergic nerves seen in peripheral arteries 12. Prolonged i m p a i r m e n t s of circulation in vascular smooth muscle could be i n d u c e d by a s u r r o u n d i n g blood clot derived from subarachnoid hemorrhage, circulatory disturbances of vasa vasorum etc.; u n d e r these conditions, the activity of m e m b r a n e ATPbase in the muscle cells and the production of ATP as a substrate would be reduced. This may result in sustained contractions of cerebral artery smooth muscle, such as is seen i n response to ouabain. The activity of Ca2+-activated Mg 2+ATPase (which is responsible for p u m p i n g Ca 2+ into intracellularly-stored sites) may also be suppressed, thus increasing the concentration of active Ca 2+ in the vicinity of the contractile proteins. PGI2, a potent e n d o g e n o u s vasodilator in h u m a n cerebral and coronary arteries, is liberated from the arterial wall by chemical and physical stimulations responsible for vasoconstriction. There is accumulating evidence that the e n d o t h e l i u m is a major site for PGI2 production 13. The endotheli u m also releases other vasodilator

Non-biased drug information H a n d b o o k of clinical pharmacology (second edition) edited by F. Bochner, T. K a m p m a n n a n d J. Brown & Company, 352 pages) I S B N 0 31

G. Carruthers, Steiner, Little, 1983. (xiii + 610064 1

This c h u b b y paperback follows the format of the 1978 edition. Its four authors are from Australia, Canada, Denmark and England, and reflect an international contribution. The suggestion that 'medical students, physicians, interns and nurses will welcome this

substances, w h e n stimulated by acetylcholine14, histamine, ADP, ATP, t h r o m b i n , etc.; the vasodilatation may be associated with lipoxygenase products and other substances yet to be identified. Therefore, functional and histological i m p a i r m e n t s of the endothelium result in a lack of buffering actions of vasodilators against vasoconstrictor interventions and, as a result, increase the ability of smooth muscle to respond with contractions. []

[]

[]

to a striking imbalance of vasoconstrictor and vasodilator regulations (Fig. 1) b y local (neural and chemical influences, atherosclerosis, endothelial lesion and dysfunction, anoxia, platelet aggregation, blood coagulation, etc) as well as systemic pathogenic factors (neural and hormonal anomalities, hypercholesterolemia, plasma Mg2+-deficiency15, alkalosis 16, etc).

References

Effects of vasoactive endogenous substances and autonomic nerve activation differ in cerebral, coronary and other vasculatures, and species differences in responses of cerebral and coronary artery are evident. It should therefore be emphasized that data obtained from experimental animals cannot always be extrapolated to healthy and diseased humans. From findings in the h u m a n arteries, it appears that the coronary artery tone is regulated b y vasoconstrictor interventions to a greater extent than is the cerebroarterial tone, whereas the latter is controlled by vasodilator interventions to a greater extent (Fig. 1). The nature and the mechanism u n d e r l y i n g cerebral and coronary artery vasospasms are thus probably quite different. The artery vasospasm is attributed possibly

1 Toda, N. (1983) J. Pharmac. Exp. Ther. 226, 861~68 2 Toda, N. (1982) Am. J. Physiol. 243, H145-H153 3 Toda, N. (1982)Circ. Res. 51,675-682 4 Toda, N., Shimizu, K. and Ohta, T. (1980)J. Neurosurg. 53. 312-322 50kamoto, S., Handa, H. and Toda, N. (1984) Stroke 15, 60~4 6 Toda, N. (1983) Am. [. Physiol. 245, H937-H941 7 Toda, N. (1981)Circ. Res. 49, 1228-1236 8 Ku, D. D. (1982)Science 218, 576-578 9 Lee, T. J.-F., Su, C. and Bevan J.A. (1975) Experientia 31, 1424-1426 10 Toda, N. (1975) J. Pharmac. Exp. Ther. 193, 376-384 11 Toda,N. (1974)Am. J. Physiol. 227, 12061211 12 Toda, N. (1980) Am. J. Physiol. 239, H199-H205 13 Toda, N. (1984) Br. J. Pharmacol. 81, 301-307 14 Furchgott, R. F. and Zawadzki, J.V. (1980) Nature (London) 288, 373--376 15 Tuflapaty,P. D. M. V. and Altura,B. M. (1980) Science 208, 198-200 16 Yasue, H., Omote, S., Takizawa, A., Nagao, M., Nosaka, K. and Nakajima, H. (1981)Am. Heart J. 102,206-210

time-saving source of essential information' is certainly appropriate. This h a n d b o o k is d i s t i n g u i s h e d however from a simple reference book b y the first eleven chapters that occupy a quarter of the book. A n introductory chapter by Professor Daniel Azarnoff, 'Do we achieve rational drug therapy?' is challenging and in effect defines one objective of the book, the provision of n o n - b i a s e d drug information. The following chapters deal with drugs and renal disease, drugs and liver disease, medication d u r i n g pregnancy, d u r i n g lactation, medication in children, in the elderly. Finally, chapter 11

offers a definition and explanation of pharmacokinetic terms. These chapters are very clearly and succinctly written and provide an exceptionally fine exposition, not readily available elsewhere. The bulk of the book, chapter 12, consists of the drug profiles of some h u n d r e d commonly used drugs, based entirely on Approved or Adopted Names arranged alphabetically. However, it is highly desirable to use the index. There are two reasons for this: the nomenclature is American (salbutamol - see albuterol), also several drugs are often listed together with a common therapeutic class (ibuprofen - see propionic acid derivatives; maprotiline - see newer antidepressants). This system of grouping of like drugs is advantageous and largely compensates for the inconvenience

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caused b y the n e e d to use the index. There are necessarily omissions, as the authors acknowledge. M u r p h y will once again validate his Law w h e n he seeks a n d fails to find the one d r u g he wanted, e.g. chlorthalidone! The selection of the most c o m m o n l y used drugs is h o w e v e r extensive a n d well-chosen. The profile for each d r u g follows a consistent pattern, a brief introduction on the action and therapeutic use, absorption, distribution, elimination, dosage schedule, therapeutic concentra-

tions, adverse reactions and interactions, together w i t h a n u m b e r of (up to 21) well-chosen references that are usefully quoted b y title. It is of interest that a figure is usually given for the biovailability of the d r u g and also for its apparent volume of distribution. In this respect the bioavailability of acetylsalicylic acid, given as 80100%, is u n d u l y high, for this does not normally exceed 68%. The figure quoted no d o u b t relates to the b i o a v a i l a b i l i t y of its metabolite, salicylic acid, w h i c h approaches 100%.

Certainly a most useful a n d valuable book; even so, most readers w o u l d surely find it even more useful if it also contained p r o p r i e t a r y names, b u t philosophies do differ. If m o m e n t a r i l y or otherwise you cannot recall the active c o m p o n e n t of 'Tagamet', alas, this h a n d b o o k will offer you no i m m e d i a t e help.

Drugs for fatties

c o m p r e h e n s i v e source of information on a relatively diffuse subject and one w h i c h is still only partially understood. That it does not completely succeed in meeting this objective is d u e in part to the complexity of the topic b u t also to a s e e m i n g lack of integration bet w e e n the various contributions. This does not a p p l y to Section II (Aspects of the Current Chemot h e r a p y of Obe~ty), containing five contributions which, taken together, cover the phenylethyla m i n e group of drugs in detail. This section is a pleasure to read. Sections I and III, covering respectively 'The O b e s e C o n d i t i o n ' a n d 'New Concepts in Obesity C h e m o t h e r a p y ' , do not represent u n i f i e d wholes, though it is difficult to see h o w this could have b e e n i m p r o v e d in Section III, w h i c h a i m e d to cover recent d e v e l o p m e n t s on all fronts relating to obesity. Section I, on the obese condition, covers the topic effectively d e s p i t e the lack of continuity. There are a few m i n o r omissions, for example, no reference was m a d e in C h a p t e r 1 to the use of electromagnetic techniques for est i m a t i o n of lean b o d y mass, a m e t h o d w h i c h is used for farm livestock and certainly deserves consideration as a n o n - i n v a s i v e m e t h o d for appraisal of o b e s i t y in man. Again, some topics have p o s s i b l y b e e n accorded less ' w e i g h t ' than they merit, such as exercise treatment and psychological treatment, both of which are d i s m i s s e d in a few lines. Section II, on aspects of the current c h e m o t h e r a p y of obesity, is an excellent review of the p h e n y l e t h y l a m i n e - r e l a t e d drugs, and there are no a p p a r e n t omis-

sions, other than one or two very recent findings. Section III also, covering n e w approaches in this area, is a valuable source of information, a n d it was pleasing to see a contribution on dietary fibre, a topic which since the appearance of this b o o k has become even more relevant to the treatment of obesity. O n the other hand, prostaglandins merited more extensive treatment than they received. There was also no reference to the n e w e r c o m p o u n d s currently u n d e r investigation in major pharmaceutical companies, despite the fact that publications on m a n y of these c o m p o u n d s have appeared. The b o o k concludes with an evaluation section which contributes little to the whole, though it is interesting to note that the Editor, in an a d d e n d u m , refers to the rise and fall of 'starch blocking' agents. It appears likely that these agents will re-emerge from the ashes in a more reputable form, and that their original fall relates more to their p r e m a t u r e commercial exploitation b y the 'pharmaceutical fringe', with resultant attention from g o v e r n m e n t agencies, than to any intrinsic lack of scientific or medical merit. Customarily in a review of this nature, one refers to misprints, quality of printing, and the like. This particular book has its share of misprints, some of which are inexcusable. For example, the last p a r a g r a p h on page 82 makes little sense, since the first line actually belongs to the last p a r a g r a p h on page 83. The correct first line of the offending p a r a g r a p h does not a p p e a r elsewhere. A n o t h e r criticism relates to the

Biochemical obesity

pharmacology

of

edited by P. B. Curtis-Prior, Elsevier Science Publishers, 1983. $140.25, Dfl330.00 (xiv + 447 pages) I S B N 0 444 80353 X

There is little d o u b t that this b o o k is a valiant effort to p r o v i d e a

B. K. MARTIN The author is Chairman of Bios (Consultancy & Contract Research) Ltd, Bagshot, UK.